Aims: To characterize potential associations of ALS with: lead exposure exposure to other neurotoxins, eg, mercury, solvents and pesticides lifestyle factors such as cigarette smoking and diet genetic polymorphisms affecting neurologic function or lead metabolism Accomplishments: Our main focus was on the relationship of ALS with lead exposure. Elevations in lead levels were associated with ALS for both bone and blood. Risk of disease increased 1.7-fold for each unit increase in blood lead, 5.3-fold for each unit increase in patella lead, and 4.2-fold for each unit increase in tibia lead. Lead levels in both cases and controls were nevertheless within the normal range. These results may suggest that chronic exposure even to small elevations in lead levels increases risk of ALS. We also found that risk of ALS was related to self-reported occupational exposure to lead. Risk of ALS was 1.9-fold greater among participants who had ever had a job involving lead exposure, and there was a dose-response for lifetime days of lead exposure. At the highest level of exposure (2000 or more days), risk of ALS was 2.3-fold greater than among unexposed participants. In contrast, risk of ALS was not associated with self-reports of either residential or recreational lead exposure. Our study is the first to use laboratory measurements as well as interview data to demonstrate an association of ALS with lead exposure. We explored the impact of diet on ALS. Although some evidence suggests that oxidative stress may play a role in ALS, we found little evidence for a protective effect of antioxidant micronutrients. Individuals in the highest quartile of lycopene intake had only half the risk of ALS. We found no relationship of ALS to dietary intake of calcium or magnesium although it has been suggested that low intake of these minerals may increase risk of ALS.